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Distinguishing autosomal‐dominant polycystic kidney disease (ADPKD) from other inherited renal cystic diseases in patients with adult polycystic kidney disease and no family history is critical for correct treatment and appropriate genetic counseling. However, for patients with no family history, there are no definitive imaging findings that provide an unequivocal ADPKD diagnosis. We analyzed 53 adult polycystic kidney disease patients with no family history. Comprehensive genetic testing was performed using capture‐based next‐generation sequencing for 69 genes currently known to cause hereditary renal cystic diseases including ADPKD. Through our analysis, 32 patients had PKD1 or PKD2 mutations. Additionally, 3 patients with disease‐causing mutations in NPHP4, PKHD1, and OFD1 were diagnosed with an inherited renal cystic disease other than ADPKD. In patients with PKD1 or PKD2 mutations, the prevalence of polycystic liver disease, defined as more than 20 liver cysts, was significantly higher (71.9% vs 33.3%, P = .006), total kidney volume was significantly increased (median, 1580.7 mL vs 791.0 mL, P = .027) and mean arterial pressure was significantly higher (median, 98 mm Hg vs 91 mm Hg, P = .012). The genetic screening approach and clinical features described here are potentially beneficial for optimal management of adult sporadic polycystic kidney disease patients. [ABSTRACT FROM AUTHOR]

Since the heat transfer characteristics in Polymer Electrolyte Fuel Cell (PEFC) influences its power generation performance, this study clarifies the temperature characteristics to in-plane direction in single PEFC. In addition, since we expect the heat and mass transfer as well as power generation characteristic are enhanced by decreasing PEM and GDL’s thicknesses, it is effective to investigate the impact of components thickness on them under high temperature operation. This study aims to clarify how to influence PEM and GDL’s thicknesses on not only heat and mass transfer characteristics but also power generation characteristic under high temperature, e.g., 90 °. The present study measured temperature distributions to in-plane direction on cathode separator back of cell by thermograph with power generation changing initial operation temperature as well as relative humidity of inflow gases. As a result, the increase in generated power and the even temperature distribution were obtained due to the decrease in GDL’s thickness. Since the moisture transfer was promoted with decreasing the thickness of PEM, the power generation performance was improved. It was clarified that the impact of GDL’s thickness was larger than that of PEM’s thickness.

Nephrotoxicity is a frequent complication of cisplatin-based chemotherapy often limiting its use. In this study, we attempted to the role of the phosphoinositide-3 kinase (PI3K)-gamma-Akt pathway in this form of acute kidney injury. Using PI3K-gamma knockout mice, we found that a conventional dose of cisplatin was more lethal in the knockout mice where the blood urea nitrogen and serum creatinine were significantly higher in them than in wild-type mice. Phosphorylation of Akt in the renal tubules was abrogated in the knockout mice with the severity of renal dysfunction and numbers of TUNEL (terminal deoxynucleotidyl transferase (TdT) mediated nick-end labeling)-positive renal tubule cells being higher in the knockout than in wild-type mice. Cisplatin treatment significantly increased. Caspase-3 activity, histone-associated DNA fragments, and number of annexin V-positive cells was significantly higher in cisplatin-treated primary cultured renal tubular epithelial cells of knockout mice. Transfection of dominant-active forms of Akt and PI3K-gamma ameliorated apoptosis of the tubule epithelial cells derived from the knockout mice. Our results suggest that the PI3K-gamma-Akt pathway lessens apoptosis and plays a critical role in the maintenance of renal function in cisplatin-induced acute kidney injury.Kidney International (2008) 73, 430-445; doi:10.1038/sj.ki.5002702; published online 28 November 2007. [ABSTRACT FROM AUTHOR]

Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable., (© 2021 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

The impact of microporous layer (MPL) on the heat- and mass-transfer characteristics and power generation performance of a polymer electrolyte fuel cell using a thin polymer electrolyte membrane (PEM) and a thin gas diffusion layer (GDL) is investigated in this paper. The power generation is investigated at the operational temperatures of 90 and 100 °C which are the target temperatures from year 2020 to 2025 according to the New Energy and Industrial Technology Development Organization's road map in Japan. The in-plane temperature distributions on the separator back at the anode and the cathode are also measured by a thermograph. As a result, it is found that the voltage drop with the MPL at a high current density is larger compared to that without the MPL irrespective of the initial temperature of the cell and relative humidity conditions. The study also revealed from the anode side observation that the in-plane temperature distribution with the MPL is wider compared to that without the MPL, especially at the initial temperature of 90 °C of the cell . Similarly, from the cathode side observation, the in-plane temperature distributions with the MPL were found to be wider compared to that without the MPL. This study has concluded that the MPL is not effective in obtaining a high performance and even an in-plane temperature distribution for a polymer electrolyte fuel cell with the thin PEM and the thin GDL at a high operational temperature range., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The inappropriate over-activation of the with-no-lysine kinase (WNK)-STE20/SPS1-related proline/alanine-rich kinase (SPAK)-sodium chloride cotransporter (NCC) phosphorylation cascade increases sodium reabsorption in distal kidney nephrons, resulting in salt-sensitive hypertension. Although chronic kidney disease (CKD) is a common cause of salt-sensitive hypertension, the involvement of the WNK phosphorylation cascade is unknown. Moreover, the effect of immune systems on WNK kinases has not been investigated despite the fact that immune systems are important for salt sensitivity. Here we demonstrate that the protein abundance of WNK1, but not of WNK4, was increased at the distal convoluted tubules in the aristolochic acid nephropathy mouse model of CKD. Accordingly, the phosphorylation of both SPAK and NCC was also increased. Moreover, a high-salt diet did not adequately suppress activation of the WNK1-SPAK-NCC phosphorylation cascade in this model, leading to salt-sensitive hypertension. WNK1 also was increased in adenine nephropathy, but not in subtotal nephrectomy, models of CKD. By comparing the transcripts of these three models focusing on immune systems, we hypothesized that tumor necrosis factor (TNF)-α regulates WNK1 protein expression. In fact, TNF-α increased WNK1 protein expression in cultured renal tubular cells by reducing the transcription and protein levels of NEDD4-2 E3-ligase, which degrades WNK1 protein. Furthermore, the TNF-α inhibitor etanercept reversed the reduction of NEDD4-2 expression and upregulation of the WNK1-SPAK-NCC phosphorylation cascade in distal convoluted tubules in vivo in the aristolochic acid nephropathy model. Thus, salt-sensitive hypertension is induced in CKD via activation of the renal WNK1- SPAK-NCC phosphorylation cascade by TNF-α, reflecting a link with the immune system., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Backgrounds: End-stage kidney disease (ESKD) is associated with increased risk of fracture and subsequent morbidity and mortality. However, fracture site-specific mortality in ESKD patients have yet to be elucidated in comparison with the general population., Methods: In this population-based cohort derived from the Diagnosis Procedure Combination database of Japan from 2012 to 2014, we included 9320 ESKD patients undergoing hemodialysis and 547,726 patients without ESKD who were hospitalized for five major fractures, including hip (proximal femur), spine, forearm, upper arm, and leg (distal femur and proximal tibia). Overall and site-specific risks of in-hospital death were determined by logistic regression models., Results: The age- and sex-adjusted mortality rates were 4.91% (95% confidence interval [CI], 4.46-5.37) and 1.02% (95% CI, 0.99-1.06) in the hemodialysis and general population groups, respectively. The multivariate odds ratio (OR) of death in hemodialysis patients versus the general population was 2.48 (95% CI, 2.25-2.74) for overall fractures, and was particularly high for a subgroup of upper arm fracture (OR 4.82, 95% CI, 3.19-7.28). The site-specific odds of death (95% CI) among hip, spine, forearm, upper arm, and leg (reference) fractures were 1.77 (0.98-3.18), 1.48 (0.79-2.75), 0.19 (0.04-0.86), and 2.01 (1.01-4.01) in hemodialysis patients, and 1.28 (1.13-1.45), 1.00 (0.88-1.14), 0.13 (0.10-0.17), and 0.83 (0.70-0.97) in the general population, respectively., Conclusion: Hemodialysis patients experienced a 4.8-fold higher mortality rate after fractures than the general population. Mortality after upper arm fracture was specifically high in patients on hemodialysis, likely due to the involvement of vascular access located on the fractured arm., (Copyright © 2019. Published by Elsevier Inc.)

Encephalopathy is a rare side effect of cephalosporin treatment. We herein present a case of encephalopathy induced by ceftriaxone, a third-generation cephalosporin, in a patient with renal failure. An 86-year-old woman on maintenance hemodialysis received ceftriaxone for Helicobacter cinaedi bacteremia. Her mental status deteriorated during antibiotic treatment, and an electroencephalogram revealed triphasic waves predominantly in the frontal area. Her consciousness improved after the discontinuation of the antibiotic due to the suspicion of ceftriaxone-induced encephalopathy. This is the first reported case of encephalopathy associated with high plasma and cerebrospinal fluid ceftriaxone concentrations, and provides significant evidence for a causal relationship between the administration of ceftriaxone and the onset of encephalopathy.

Autoimmune neurological diseases are often treated by immunoadsorption using a conventional plasma separator and tryptophan-immobilized column (IA). However, there is only one case report on treatment with immunoadsorption using a selective plasma separator and tryptophan-immobilized column (SeIA) in clinical practice. This study aimed to investigate the removal characteristics of antibodies against acetylcholine receptors (AChRAb), immunoglobulin G, fibrinogen, and factor XIII (FXIII) in IA and SeIA in four patients with myasthenia gravis. A total of 19 sessions of immunoadsorption were performed (five sessions of IA and 14 sessions of SeIA) when the processed plasma volume was 2 L. The corresponding reductions were 52.5% ± 6.2% for AChRAb, 58.8% ± 4.2% for fibrinogen, and 36.9% ± 5.5% for FXIII after one session of IA. The corresponding reductions were 45.2% ± 9.9% for AChRAb, 3.5% ± 6.9% for fibrinogen, and -4.6% ± 11.1% for FXIII after one session of SeIA. The removal rates for AChRAb, fibrinogen, and FXIII in IA were significantly higher than those in SeIA. IA could effectively remove AChRAb, and SeIA could retain fibrinogen and FXIII. IA can be combined with SeIA, resulting in both IgG autoantibodies removal by IA and retention of coagulation factors by SeIA., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

The kidneys consume a large amount of energy to regulate volume status and blood pressure and to excrete uremic toxins. The identification of factors that cause energy mismatch in the setting of chronic kidney disease (CKD) and the development of interventions aimed at improving this mismatch are key research imperatives. Although the critical cellular energy sensor 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is known to be inactivated in CKD, the mechanism of AMPK dysregulation is unknown. In a mouse model of CKD, metabolome analysis confirmed a decrease in AMPK activation in the kidneys despite a high AMP: ATP ratio, suggesting that AMPK did not sense energy depletion. Similar AMPK inactivation was found in heart and skeletal muscle in CKD mice. Several uremic factors were shown to inactivate AMPK in vitro and in ex vivo preparations of kidney tissue. The specific AMPK activator A-769662, which bypasses the AMP sensing mechanism, ameliorated fibrosis and improved energy status in the kidneys of CKD mice, whereas an AMP analog did not. We further demonstrated that a low-protein diet activated AMPK independent of the AMP sensing mechanism, leading to improvement in energy metabolism and kidney fibrosis. These results suggest that a failure to sense AMP is the key mechanism underlying the vicious cycle of energy depletion and CKD progression and direct AMPK activation may be a novel therapeutic approach in CKD., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Pseudohypoaldosteronism type II (PHAII) is a hereditary hypertensive disease caused by mutations in four genes: WNK1, WNK4, Kelch-like3 (KLHL3), and cullin3 (CUL3). Recently, it was revealed that CUL3-KLHL3 E3 ligase complex ubiquitinates WNK1 and WNK4, leading to their degradation, and that a common pathogenesis of PHAII is defective WNK degradation due to CUL3-KLHL3 E3 ligase complex impairment. PHAII-causing CUL3 mutations mediate exon9 skipping, producing a CUL3 protein with a 57-amino acid deletion (Δ403-459). However, the pathogenic effects of KLHL3, an adaptor protein that links WNKs with CUL3, in PHAII caused by CUL3 mutation remain unclear., Methods: To clarify detailed pathophysiological mechanisms underlying PHAII caused by CUL3 mutation in vivo, we generated and analyzed knock-in mice carrying the same CUL3 exon9 deletion (CUL3 WT/Δex9 ) as that reported in PHAII patients., Results: CUL3 WT/Δex9 mice exhibited a PHAII-like phenotype. Interestingly, we confirmed markedly decreased KLHL3 expression in CUL3 WT/Δex9 mice by confirming the true KLHL3 band in vivo. However, the expression of other KLHL family proteins, such as KLHL2, was comparable between WT and mutant mice., Conclusion: KLHL3 expression was decreased in CUL3 WT/Δex9 mice. However, expression levels of other KLHL family proteins were comparable between the wild-type and mutant mice. These findings indicate that the decreased abundance of KLHL3 is a specific phenomenon caused by mutant CUL3 (Δexon9). Our findings would improve our understanding of the pathogenesis of PHAII caused by CUL3 mutation in vivo.

In patients with chronic kidney disease (CKD), low body mass index (BMI) is associated with high mortality. This relationship in emergently hospitalized CKD patients is unknown. We investigated the association between obesity and short-term mortality in emergently admitted patients with dialysis-independent CKD (DI-CKD) with and without infection. This retrospective cohort study examined Diagnosis Procedure Combination data of 26103 emergently hospitalized DI-CKD patients. Patients were divided into 8 groups according to their BMI and the presence of infectious diseases. The primary outcome was in-hospital death within 100 days. Cox proportional hazards models adjusted for baseline characteristics showed that low BMI was associated with the outcome both in infected and in non-infected patients (reference group as non-infected and medium BMI [24-26 kg/m2] group): infected and the lowest BMI (≤20 kg/m2) group, hazard ratio (HR) 1.82 (95% confidence interval 1.51, 2.19); non-infected and the lowest BMI group, 1.39 (1.16, 1.67). When patients were stratified according to presence of diabetes mellitus (DM), patients with DM showed that low BMI was associated with the outcome both in infected and in non-infected patients, whereas in non-DM patients, this relationship was attenuated in the non-infected group. For emergently hospitalized CKD patients with infection, high BMI was associated with lower mortality irrespective of the DM status. For non-infected patients, the effects of obesity for in-hospital mortality were modified by the DM status., Competing Interests: The authors have declared that no competing interests exist.

Background: Perioperativemanagement of hemodialysis patients involves many difficulties. High mortality rate and circulatory or respiratory complications in these patients were reported. However, in such reports, there is no concrete information of perioperative management in hemodialysis patients to prevent surgical complications and successful outcomes., Case Presentation: We retrospectively reviewed the cases of 5 hemodialysis patients who underwent oral surgery under general anesthesia between January 2005 and December 2017. Primary disease was oral squamous cell carcinoma (SCC) in 4 patients and mandibular ameloblastoma in 1 patient. Partial resection was performed in 2 cases, neck dissection in 1 case. Two cases underwent surgery including vascularized reconstruction. The patients were dialyzed the day before and after surgery for the control of fluid and electrolyte status. Patients received intraoperative and postoperative intravenous infusion of potassium-free solution at 20-40 mL/h. Erythropoiesis-stimulating agents (ESAs) were used on the day of hemodialysis during hospitalization. Nafamostat mesilate as an anticoagulant during hemodialysis were used from postoperative day (POD)1 to 7. From POD 1 to 10, cephalosporin as prophylactic antibiotics is adjusted to quarter from half the initial dose. The resuming time of oral intake was similar to that of other oral surgery patients without kidney disease. The daily intake limits of protein, salt and liquid were managed during hospitalization and no cases suffered from malnutrition. No cardiorespiratory complications occurred during the perioperative period. In a case of vascularized osteocutaneous scapular flap reconstruction, grafted scapular bone survived and scapular cutaneous flap necrotized. Necrotic tissue was debrided and split thickness skin was successfully used to cover the grafted scapular bone., Conclusions: Postoperative better result could be achieved if adequate perioperative management specific to hemodialysis patients is carried out. Vascularized flap reconstruction at oral and maxillofacial region in hemodialysis patients is beneficial treatment. Even if the first flap has wound complication secondary flap reconstruction is success and aesthetically better results could be achieved by the strict wound management and debridement.

Objective: Metformin is an antidiabetic drug that is widely used to treat patients with diabetes mellitus. Recent studies have reported that treatment with metformin not only improved blood glucose levels but also reduced blood pressure. However, it remains unclear how metformin reduces blood pressure. We hypothesized that metformin affects sodium reabsorption in the kidneys., Methods: Urinary sodium excretion and expression of renal sodium transporters were examined in 8-week-old male C57BL/6 mice with acute and chronic treatment of metformin. In addition, we examined metformin effects using ex vivo preparations of mice kidney slices., Results: In this study, we demonstrated that metformin increased urinary sodium excretion by reducing phosphorylation of the thiazide-sensitive Na-Cl cotransporter (NCC) in acute and chronic metformin administration. We also confirmed reduction of phosphorylated NCC in an ex vivo study. The activity of other renal sodium transporters, such as NKCC2, ENaC, and NHE3 did not show significant changes. WNK-OSR1/SPAK kinase signals were not involved in this inactivation effect of metformin on NCC., Conclusion: Metformin increased urinary sodium excretion by reducing phosphorylation of NCC, suggesting its role in improving hypertension., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Selective plasma exchange has been shown to be effective in various diseases, but no studies have assessed the benefits of daily treatment. We aimed to investigate the removal dynamics of immunoglobulins, fibrinogen, and factor XIII on three consecutive days in three patients. For mean processed plasma volumes of 1.06 × plasma volume, reductions of 79.6%, 49.3%, and 8.6% were seen for immunoglobulins G, A, and M, respectively. The reductions for fibrinogen and factor XIII were 18.4% and 13.0%, respectively. Removal dynamics were similar for immunoglobulin G-related autoantibodies and immunoglobulin G when using daily selective plasma exchange. Moreover, daily use effectively removed the immunoglobulin G while retaining the coagulation factors. When disease-specific autoantibodies are limited to immunoglobulin G, daily selective plasma exchange may be a useful and safe method of intensive induction treatment for plasmapheresis. However, further study is required in larger cohorts to confirm these findings., (© 2018 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)